Clean Rooms and Air Handling Systems — Design for Compliance - Pharmaceutical Technology

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Clean Rooms and Air Handling Systems — Design for Compliance
This article provides an overview of the important factors associated with air handling systems within pharmaceutical and biopharmaceutical facilities. It provides information on the need for these systems, design considerations and advice on the approach to commissioning and qualification.


Pharmaceutical Technology Europe


The design, installation, commissioning and qualification of clean rooms heating, ventilation and air conditioning (HVAC) systems is often one of the largest considerations in the design of a new pharmaceutical or biotechnology manufacturing facility. With high running costs (energy associated with the movement, cooling and heating of air) and the potential to impact upon safety and product quality, getting them right
is important for business, safety and good manufacturing practice (GMP) criticality.

The design of the HVAC system will be based upon the clean room suite that it serves, and will be affected by factors such as the number of rooms served, the layout of the rooms, the equipment within the rooms and, most critically from a qualification perspective, the environmental conditions that the rooms must achieve.

Background

The air handling unit helps maintain each room's clean environment by providing an appropriate volume of clean air to each room at the correct temperature and humidity.

The air is filtered by pleated paper filters called high efficiency particulate air (HEPA) filters which, depending upon the classification of the rooms, are located either within the air handling unit or where the air enters each room. Cooling and heating coils are also located within the air handling unit, increasing or decreasing the air temperature to ensure that the room temperatures remain within specification.

Reliable operation of the air handling unit within established limits is critical,1 not only to prevent product quality from
being compromised by poor air conditioning, but also for the following reasons:

  • to prevent cross contamination of products
  • to maintain operator safety, where the HVAC is being used for this purpose
  • to maintain product safety, where the HVAC is being used for this purpose.

Defining the Requirements


Figure 1 The cost of change during a project, based on the stage of the project.
Whereas other services and utilities can be (relatively) easily moved within a building's framework once the building work has been completed, the HVAC is much more integral with the building's fabric, making retrospective modifications much more time consuming and expensive. Getting the specification and design right first time is very important. Figure 1 shows how the costs involved in changing a design increase dramatically as a project progresses.

What are the problems?

If the design phase is completed without considering the compliance aspects of the clean rooms, then there is a high likelihood of incurring significant time delays and costs during the validation period, as a result of having to make mechanical changes to the installation or revisiting some of
the commissioning work.

Some typical examples of areas where problems can occur as a result of not designing for compliance are highlighted below, together with suggested actions to try to avoid these problems from occurring.

Operating tolerances. Design, commissioning and validation criteria must be determined for GMP-critical parameters such as air change rates, room differential pressures, temperature and humidity.1 For example, different tolerances may need to be applied at commissioning and validation to ensure that the facility will operate reliably within the validation acceptance criteria limits.

Air filtration. The level of air filtration will vary depending upon the classification of the clean rooms being served. For example, an ISO Class 5 room (Class 100) will require terminal HEPA filters, whereas an ISO Class 8 environment (Class 100000) may be achieved by using a high-grade (non-HEPA) filter within the air handling unit.2 To avoid failures during validation integrity testing it is important for the validation and design teams to discuss the in situ test requirements, and to agree upon appropriate grades of air filtration.


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